The prevalence of diabetes mellitus (DM) and obstructive sleep apnea (OSA) are increasing rapidly with the current epidemic of obesity in the United States. Both DM and OSA are associated with autonomic dysfunction, increasing the risk of sudden death and cardiovascular disease in these disorders. Additional links between these disorders exist as well, as OSA is associated with a significantly higher prevalence of impaired glucose regulation (undiagnosed diabetes, impaired glucose tolerance, or impaired fasting glucose collectively called IGR for the purpose of this study). The current model is that OSA causes increased sympathetic activity secondary to intermittent hypoxia. Controversy exists, however, as to whether OSA causes autonomic dysfunction via hyperglycemia, or whether damage to the autonomic nervous system through hyperglycemia causes sleep apnea. My hypothesis is that IGR resulting from OSA is an independent cause of autonomic dysfunction in these patients. The goals of this proposal are to answer the questions: 1) Does autonomic dysfunction occur in OSA independently of IGR and 2) What is the effect of continuous positive airway pressure (CPAP) therapy on glucose regulation and autonomic function. My specific aims are 1) Define whether autonomic dysfunction in patients with OSA is directly associated with OSA or is secondary to IGR; 2) Determine if there is associated peripheral nerve dysfunction in OSA subjects with IGR; and 3) Evaluate the effect of CPAP on glucose and autonomic function in a six-month longitudinal study. The training component of my proposal will consist of learning new methodology in assessment of autonomic and peripheral nerve physiology, and in designing and implementing a longitudinal study. As part of my training, I will learn techniques such as spectral analysis of heart rate variability and evaluation of intraepidermal nerve fiber density in skin biopsies. My progress will be followed by my mentors, Drs. Beth Malow and Stephen Davis, and by consultants Drs. Eva Feldman and David Robertson. This career development award will allow me to achieve my long-term goal of becoming a clinician-scientist specializing in neuromuscular disorders. [unreadable] [unreadable] [unreadable]